Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic erythematosus patients

Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
Lupus (Impact Factor: 2.2). 11/2009; 19(3):317-22. DOI: 10.1177/0961203309348983
Source: PubMed


Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

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    • "Today, it is well accepted that MSCs have important immunosuppressive properties over the entire immune system , mainly exerting their effects on T, B, NK, and dendritic cells [8] [9]. This immunomodulatory capacity of MSCs has opened new therapeutic prospects in the management of proinflammatory and autoimmune pathologies [10] [11] [12]. The therapeutic potential of MSCs has been demonstrated in a variety of autoimmune disease models including graftversus-host disease (GVDH) [13], experimental autoimmune encephalomyelitis (EAE) [14] [15], collagen-induced arthritis "
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    ABSTRACT: The Silences of the Archives, the Reknown of the Story. The Martin Guerre affair has been told many times since Jean de Coras and Guillaume Lesueur published their stories in 1561. It is in many ways a perfect intrigue with uncanny resemblance, persuasive deception and a surprizing end when the two Martin stood face to face, memory to memory, before captivated judges and a guilty feeling Bertrande de Rols. The historian wanted to go beyond the known story in order to discover the world of the heroes. This research led to disappointments and surprizes as documents were discovered concerning the environment of Artigat’s inhabitants and bearing directly on the main characters thanks to notarial contracts. Along the way, study of the works of Coras and Lesueur took a new direction. Coming back to the affair a quarter century later did not result in finding new documents (some are perhaps still buried in Spanish archives), but by going back over her tracks, the historian could only be struck by the silences of the archives that refuse to reveal their secrets and, at the same time, by the possible openings they suggest, by the intuition that almost invisible threads link here and there characters and events.
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    • "The FoxP3 expression and Treg function have been linked with hemoxygenase-1 (HO-1), which is implicated in the activation as well as induction and/or expansion of Tregs, as it is constitutively expressed in human peripheral blood Tregs but not in resting CD4+CD25− non-Tregs [23], [24], [25], [26], [27], [28], [29]. Since HO-1 derived carbon monoxide can induce the DosR dormancy regulon in mycobacteria, leading to latency and survival of this organism inside the host granuloma, we hypothesized that such a situation could contribute to 20–30 times higher lifetime risk of developing active tuberculosis in HIV infected individuals. "
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    PLoS ONE 09/2014; 9(9):e106815. DOI:10.1371/journal.pone.0106815 · 3.23 Impact Factor
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    • "However, studies performed on patients of autoimmune diseases have demonstrated the advantage of using allogeneic MSC. The Using of autologous MSC did not seem to improve SLE disease course despite an increase of proportion of peripheral blood T-regs.86 MSC extracted from SLE patients grew slower in culture, display less viability and produce less TGF-β in contrast to allogeneic healthy MSC indicating that the former cells are probably defective in function.87 "
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